ABSTRACT: Chronic migraine is a disabling complication of migraine with headaches that occurs 15 or more days per month. Patients with chronic migraine frequently experience medication overuse headaches that may further complicate this disorder and cause more problems for clinically treating headaches. Since the pain of a patient with chronic migraine typically worsens with physical activity and is often refractory to standard treatment, patients with chronic migraine have very low qualities of life which in term greatly impacts society. One of the most important advances in migraine research is the confirmation of cortical hyper- and hypo- activation with non-invasive neuroimaging technologies such as magnetoencephalography (MEG). MEG study of migraine has shown that the normalization of cortical activation can reduce the incidence of migraine attacks. Antiepileptic drugs (AED), which may change cortical activation, are frequently effective in the prevention of migraine. However, cortical dysfunction in chronic headaches can be hyper- or hypo-activation which depends on the pathology and brain regions. The underlying cerebral mechanism is poorly understood and has rarely been studied in pediatric chronic migraine. We hypothesize that pediatric chronic migraine is associated with cortical hyper- and hypo-activation in a set of brain areas. This hypothesis is based on the observations that the location and degree of cortical excitability in acute migraine have been quantitatively and noninvasively determined with advanced MEG methods such as beamforming and wavelet. Building on our research experience in migraine and MEG, we propose to address the following specific aims: (1) quantify the spatiotemporal and spectral signatures of aberrant brain activation in children with chronic migraine during headache attacks with MEG; (2) determine the spatiotemporal and spectral changes of brain activation in children with chronic migraine before, during and after clinical treatment. The innovation of the present study is the measurements of very high-frequency neuromagnetic signals (up to 2884 Hz) in chronic migraine because MEG study of migraine is conventionally limited to a low-frequency range (< 70 Hz). Since high-frequency neuromagnetic signals are well localized to focal brain areas, if successful, we can precisely determine with high-frequency MEG data in the proposed study where and to what degree cortical activation changed in chronic migraine. With a clearer understanding of the location and types of aberrant cortical activation occurring, all of the treatments targeted at cortical excitability (e.g. AED, transcranial magnetic stimulation, transcranial direct current stimulation, acupuncture) - which currently show great promise -could be specified, refined and their outcomes significantly improved. Given that high-frequency neuromagnetic signals are a new biomarker, a more in-depth study of chronic migraine with advanced MEG methods is a critical next step in our understanding of migraine pathophysiology and our ability to develop better treatment and prevention strategies.